Administration of 5-HT1 receptor agonist, m-chlorophenylpiperazine (m-CPP) to rats produced dose-dependent decreases in food intake, locomotor ac- tivity, and hyperthermia, increases in plasma prolactin and corticosterone, and a decrease in plasma growth hormone. Long-term treatment with clomipramine (a tricyclic antidepressant as well as an antiobsessive- compulsive agent) potentiated the effect of M-CPP on plasma prolactin concentrations but not on food intake or locomotor activity, and also attenuated the effect of M-CPP on temperature and plasma corticosterone concentrations. Long-term treatment with lithium (antimanic and antidepressant agent) attenuated the effect of M-CPP on food intake but not locomotor activity. These findings indicate that various agents effective in different types of affective disorders exert differential modulatory influences on serotonergic mechanisms regulating food intake, locomotor activity, temperature, and neuroendocrine changes In vivo. In another study, therapeutic concentrations of lithium (1-1.5 mM in vitro) inhibited the function of Gs protein in the cerebral cortex of the rat, while 4- to 8-fold larger concentrations of lithium were required to alter the function of Gs protein equivalently in the cardiac ventricles of the rat. Chronic administration of lithium to rats totally abolished the effect of isoproterenol on the binding of guanosine triphosphate (GTP) in the CNS but did not affect the function of peripheral cardiac Gs protein. The lithium-selective action on the function of Gs protein in the CNS may stem from the heterogeneity of the alpha subunit proteins: in the heart, the major species is a 45 kDa molecule, while in the brain, a 52 kDa molecular weight species predominates. The heterogeneity in alpha subunits may thus be the biochemical basis for the selective action of lithium on the CNS and for the scarcity of peripheral side effects.